Developmental toxicity to TCDD-like congeners in fish, birds, and mammals, and reproductive toxicity in mammals are reviewed. In fish and bird species, the developmental lesions observed are species dependent, but any given species responds similarly to different TCDD-like congeners. Developmental toxicity in fish resembles "blue sac disease," whereas structural malformations can occur in at least one bird species. In mammals, developmental toxicity includes decreased growth, structural malformations, functional alterations, and prenatal mortality. At relatively low exposure levels, structural malformations are not common in mammalian species. In contrast, functional alterations are the most sensitive signs of developmental toxicity. These include effects on the male reproductive system and male reproductive behavior in rats, and neurobehavioral effects in monkeys. Human infants exposed during the Yusho and Yu-Cheng episodes, and monkeys and mice exposed perinatally to TCDD developed an ectodermal dysplasia syndrome that includes toxicity to the skin and teeth. Toxicity to the central nervous system in monkey and human infants is a potential part of the ectodermal dysplasia syndrome. Decreases in spermatogenesis and the ability to conceive and carry a pregnancy to term are the most sensitive signs of reproductive toxicity in male and female mammals, respectively.

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The limitations of somatosensory evoked potentials during aortic occlusion stimulated us to evaluate the sensitivity and specificity of spinal (T10 and L4) evoked potentials (SpEPs) in predicting neurologic function after aortic occlusion. Thirty-six swine were assigned randomly to three equal groups (Group 1, control; Group 2, cerebrospinal fluid (CSF) drainage; Group 3, CSF drainage with 20-mg intrathecal papaverine). After induction of anesthesia and initiation of physiologic monitoring, a left-sided thoracotomy was performed to provide access to the descending aorta. SpEPs were generated by stimulating the thoracic spinal cord and recording the conducted response at the T10 and L4 level. After baseline measurements were recorded, the descending aorta was occluded 1 cm distal to the left subclavian artery. SpEPs were recorded every 2.5 min and physiologic variables every 5 min. The aorta was unclamped 10, 15, or 20 min after loss of the L4 SpEP. If the L4 SpEP was not lost, the aortic occlusion interval was terminated at 90 min. Attenuation of the SpEPs occurred earlier at the L4 level. Group 1 experienced the earliest loss of the L4 SpEP (18.3 +/- 7.8 min, P < 0.005). Loss of the L4 SpEP in Group 2 (49.3 +/- 27.8 min) was earlier than in Group 3 (73.7 +/- 26.1 min, P < 0.05). Early postoperative motor function (modified Tarlov scale) correlated with time from loss of the L4 SpEP until reperfusion of the distal aorta (r = 0.93). The sensitivity, specificity, and accuracy of the L4 SpEP in predicting neurologic dysfunction was 92.8% (13 abnormal/14 predicted), 90.9% (20/22), and 91.7% (33/36).(ABSTRACT TRUNCATED AT 250 WORDS)

Optogenetics promises spatiotemporal precise control of neural processes using light. However, the spatial extent of illumination within the brain is difficult to control and cannot be adjusted using standard fiber optics. We demonstrate that optical fibers with tapered tips can be used to illuminate either large brain volumes or dynamically selectable subregions.Remotely adjusting the light input angle to the fiber varies the light-emitting portion of the taper over several millimeters without movement of the implant. We use this mode to activate dorsal versus ventral striatum of individual mice and reveal different effects of each manipulation on motor behavior. Conversely injecting light over the full numerical aperture of the fiber results in light emission from the entire taper surface, achieving broader and more efficient optogenetic activation of neurons when compared to the standard flat-faced fiber stimulation. Thus, tapered fibers permit focal or broad illumination that can be precisely and dynamically matched to experimental needs.

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